Acute myeloid leukemia - challenges 2024

Acute myeloid leukemia is said to be an uncomplicated disease affecting the elderly. What makes up the clinical picture of this disease?

It is a disease that occurs suddenly in many patients in full health. In most, it actually falls like a bolt from the blue. It can be contracted at any age. Children also get sick. On the other hand, the incidence of this disease increases with age. In addition, there is no very characteristic clinical picture for it, which would indicate from the beginning that it is acute myeloid leukemia, or any acute leukemia. The disease begins somewhat insidiously, as very often the first symptoms are related to infections. At first they are a little bit ignored by the patient himself, or... I don't want to say by the family doctor, but it is approached quite calmly. These are symptoms of either upper or lower respiratory tract infections, but which often do not yield to treatment. It's also increasing weakness, feverish states without a specific cause, poor exercise tolerance. It's even a tendency to bleed and bruise easily, what we call hemorrhagic diathesis. And this is perhaps the most worrisome symptom for patients. Ordering a blood count at this point does not diagnose the disease, but it does indicate the subsequent course of treatment. For a hematologist, looking at even a CBC can be helpful to indicate acute leukemia (without a detailed diagnosis, of course). It is also clear to the family physician, who usually refers such patients to hematology centers as a matter of urgency. This speed of referral and diagnosis is very important. For me, acute myeloid leukemia is a life-threatening condition, not because it's a malignancy and like any such disease is a threat, but it is an immediate life-threatening one. We need to make a diagnosis in a short period of time and seek treatment in a short period of time. It is a very heterogeneous disease: heterogeneous in its clinical picture, but also in terms of its biological picture. That is, the course of the disease varies from patient to patient, but also its characteristics of biology, the nature of the tumor (leukemic) cell, is different. Today we make strong use of genetic testing, which allows us to determine the subtype of the disease, but also to choose a therapy. This is very important, because more and more we are reaching for targeted drugs that literally like a key to a lock fit certain changes, disorders seen in acute leukemia, and which more easily allow us to fight the disease.

So what are the diagnostic and therapeutic challenges in acute myeloid leukemia?

I mentioned that this is a disease that needs to be diagnosed quickly and start treating it quickly. To treat it faster, we need to have drugs on the shelf and access to all therapies that are effective and registered. We need to start with diagnostics. If genetic diagnosis is needed, this is the biggest challenge, because it should not take more than 3-5 days to do a professional genetic diagnosis for acute myeloid leukemia. These are the international and European guidelines. I want to say that today we have it! And in many centers that treat acute myeloid leukemia, our teams can make a diagnosis in no time. We have the genetic, molecular profile assessed within days, and this allows us to choose targeted therapy. We have more and more drugs that we add, or not, to standard chemotherapy, intensive chemotherapy (depending on the patient's clinical situation). We base the inclusion of this treatment precisely on the results of genetic testing. One drug, a treatment regimen, we are sorely lacking, which consists of an IDH1 inhibitor and azacitidine. The treatment, which is already registered in the world, the US and the EU (it is not reimbursed in our country) is for maybe not a very large group of patients, but for patients who do not qualify for intensive therapy, who show some genetic abnormality in their disease, and who respond very well to this treatment, as we know from the registration study.

What are the results of clinical trials?

The results show that the therapy repeatedly improves survival, response rates, overall survival, prolongs disease remission time, and improves quality of life. And it is, in addition, a very safe therapy compared to other forms of treatment. We talk all the time about very intensive hematological treatment in acute blood disease, so when we say safe, we don't mean ideal. Compared to other forms of treatment, this is a therapy that brings us closer indeed to almost complete outpatient treatment, although not 100 percent and not in every patient.

There were a lot of positive reimbursement decisions in hemtooncology last year. Is the treatment you are talking about one of this year's priorities?

At the moment, this is the main treatment we care about. Because for a certain group of patients, we don't have a targeted therapy that we know is very good, that we know is effective and safe.